PMID- 30644695 OWN - NLM STAT- MEDLINE DCOM- 20190912 LR - 20190912 IS - 1735-1502 (Print) IS - 1735-1502 (Linking) VI - 17 IP - 6 DP - 2018 Dec 2 TI - Elevated Expression of Tim-3 and PD-1 Immune Checkpoint Receptors on T-CD4+ Lymphocytes of Patients with Asthma. PG - 517-525 AB - Asthma is a chronic disorder of the airways characterized by reversible airflow obstruction, inflammation and bronchial hyperresponsiveness. Different immune cells and molecules have been attributed to involve in pathogenesis of asthma. In the current case-control study, the expression of T cell Ig and mucin domain-containing molecule-3 (Tim-3) and programmed death-1 (PD-1) was studied on CD4+ T cells of patients with asthma and normal controls. The frequency of Tim-3+/PD-1+/CD4+ T cells was determined by a three color flow cytometry method in 37 patients with asthma and 32 healthy controls. To evaluate the Th1/Th2 ratio, peripheral blood mononuclear cells were isolated from all samples and stimulated with phorbol 12- myristate 13- acetate ( PMA)/ionomycin for 18 h. IFN-gamma) and Interleukin-4 (IL-4) were measured in culture supernatants by-(ELISA). Serum total immunoglobulin E (IgE) was also measured in all samples. Significant increase in percentage and absolute count of Tim-3+/PD-1+/CD4+, Tim-3+/CD4+ and PD-1+/CD4+ T cells was found in asthmatic patients compared to healthy controls (p=0.02 and p=0.003, respectively). The IFN-gamma/IL-4 ratio (Th1/Th2 ratio) was significantly higher in healthy controls than that of asthmatic patients (p=0.029). Our data regarding the increased expression of PD-1 and Tim-3 on CD4+ T cells of patients with asthma suggest the potential roles of these immune checkpoint receptors in immune dys-regulation of asthma. FAU - Mosayebian, Ali AU - Mosayebian A AD - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. ali.mosayebian@gmail.com. FAU - Koohini, Zohreh AU - Koohini Z AD - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. z.koohini@gmail.com. FAU - Hossein-Nataj, Hadi AU - Hossein-Nataj H AD - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. hadi.nataj2000@gmail.com. FAU - Abediankenari, Saeid AU - Abediankenari S AD - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. abedianlab@yahoo.co.uk. FAU - Abedi, Siavash AU - Abedi S AD - Department of Internal Medicine, Pulmonary and Critical Care Division, Mazandaran University of Medical Sciences, Sari, Iran. siavash.abedi0@gmail.com. FAU - Asgarian-Omran, Hossein AU - Asgarian-Omran H AD - Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. asgarianhossein@yahoo.com. LA - eng PT - Journal Article DEP - 20181202 PL - Iran TA - Iran J Allergy Asthma Immunol JT - Iranian journal of allergy, asthma, and immunology JID - 101146178 RN - 0 (HAVCR2 protein, human) RN - 0 (Hepatitis A Virus Cellular Receptor 2) RN - 0 (IL4 protein, human) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Adult MH - Asthma/*immunology MH - CD4-Positive T-Lymphocytes/*metabolism MH - Case-Control Studies MH - Cells, Cultured MH - Female MH - Flow Cytometry MH - Hepatitis A Virus Cellular Receptor 2/*metabolism MH - Humans MH - Immunophenotyping MH - Interleukin-4/metabolism MH - Male MH - Middle Aged MH - Programmed Cell Death 1 Receptor/*metabolism MH - Up-Regulation OTO - NOTNLM OT - Asthma OT - Interferon-gamma OT - Interleukin-4 OT - PD-1 OT - Tim-3 EDAT- 2019/01/16 06:00 MHDA- 2019/09/13 06:00 CRDT- 2019/01/16 06:00 PHST- 2017/12/04 00:00 [received] PHST- 2018/05/01 00:00 [accepted] PHST- 2019/01/16 06:00 [entrez] PHST- 2019/01/16 06:00 [pubmed] PHST- 2019/09/13 06:00 [medline] PST - epublish SO - Iran J Allergy Asthma Immunol. 2018 Dec 2;17(6):517-525.